Lymphadenopathy Workup

Updated: Mar 03, 2020
  • Author: Vikramjit S Kanwar, MBBS, MBA, MRCP(UK), FAAP; Chief Editor: Russell W Steele, MD  more...
  • Print

Laboratory Studies

The laboratory evaluation of lymphadenopathy must be directed by the history and physical examination and is based on the size and other characteristics of the nodes and the overall clinical assessment of the patient. When a laboratory evaluation is indicated, it must be driven by the clinical evaluation. [1]

The following studies should be considered for chronic lymphadenopathy (>3 wk):

  • CBC count, including a careful evaluation of the peripheral blood smear

  • Lactate dehydrogenase (LDH) and uric acid

  • Chest radiography

  • B henselae (catscratch) serology if exposed to a cat

  • Tuberculosis skin test (TST) and interferon-gamma release assay (eg, Quantiferon Gold)

Evaluation of hepatic and renal function and a urine analysis are useful in identifying underlying systemic disorders that may be associated with lymphadenopathy. When evaluating specific regional adenopathy, lymph node aspirate for culture may be important if lymphadenitis is clinically suspected.

Titers for specific microorganisms may be indicated, particularly if generalized adenopathy is present. These may include Epstein-Barr virus, cytomegalovirus (CMV), Toxoplasma species, and human immunodeficiency virus (HIV).


Imaging Studies

Chest radiography may be helpful in elucidating mediastinal adenopathy and underlying diseases affecting the lungs, including tuberculosis, coccidioidomycosis, lymphomas, neuroblastoma, histiocytoses, and Gaucher disease. [2]

Supraclavicular adenopathy, with its high associated rate of serious underlying disease, may be an indication for computed tomography (CT) scan of the chest, abdomen, or both.

A retrospective study by Razek et al indicated that diffusion-weighted magnetic resonance imaging (MRI) can be used to differentiate malignant from benign mediastinal lymphadenopathy in children. In the study, which included 29 children with mediastinal lymphadenopathy, patients were assessed with single-shot echo planar diffusion-weighted MRI, with the mean apparent diffusion coefficient (ADC) for the malignant condition being significantly below that for benign mediastinal lymphadenopathy. [18]  However, although this study may represent an important advance in the imaging of mediastinal/hilar lymphadenopathy, the results must be confirmed before the routine use of this technique can be recommended.

Positron-emission tomography (PET) scanning is not helpful as a screening tool as benign and malignant conditions may cause intense uptake. [19] However, PET scanning is helpful in the staging of lymphomas once a diagnosis is made. [20]

Ultrasonography may be helpful in documenting the extent of lymph node involvement and any changes in the lymph nodes. [21] In children with inguinal adenopathy or abdominal complaints, ultrasonography of the abdomen, CT scan of the abdomen, or both may be indicated. [22] Ultrasonography is rarely of diagnostic value for lymphadenopathy in childhood, even with advanced techniques. [23]

A study by Ying et al indicated that evaluation of the intranodal vascularity index is an effective means of diagnosing metastatic and tuberculous lymph nodes in patients with cervical lymphadenopathy. Using ultrasonographic images from 347 patients with palpable cervical lymph nodes, a customized computer program was used to quantify the intranodal vascularity index. With regard to distinguishing metastatic and tuberculous lymph nodes, the index was found to have a sensitivity and specificity of 80% and 73%, respectively; positive and negative predictive values of 91% and 51%, respectively; and an overall accuracy of 68%, when the cutoff vascularity index was 22%. [24]

A study by Tan et al indicated that shear-wave elastography (SWE) is an effective imaging modality for distinguishing benign from malignant superficial lymphadenopathy when the distinction cannot be made using conventional ultrasonography. The investigators found that in malignant lesions, the maximum and mean elastic modulus, as well as the standard deviation of the elastic modulus, were significantly higher than for benign lesions. [25]



The critical question is often whether or not to perform a lymph node biopsy; this requires an overall assessment of the history and physical examination as described above.

Images taken during and after a lymph node biopsy are shown below.

A lymph node biopsy is performed. Note that a mark A lymph node biopsy is performed. Note that a marking pen has been used to outline the node before removal and that a silk suture has been used to provide traction to assist the removal.
A lymph node after removal by means of biopsy, whi A lymph node after removal by means of biopsy, which was performed completely under a local anesthetic technique.
A gross image of a node following excision. The cu A gross image of a node following excision. The cut surface of the node shows the typical fish-flesh appearance seen with lymphoma.

Treatment with antibiotics covering bacterial pathogens frequently implicated in lymphadenitis, followed by reevaluation in 2-4 weeks is reasonable, if clinical findings suggest lymphadenitis. Benign reactive adenopathy may be safely observed for months. [8]

If the size, location, or character of the lymphadenopathy suggests malignancy, the need for laboratory studies and biopsy is more urgent. If laboratory testing is inconclusive, a lymph node biopsy is immediately indicated.

Fine needle aspiration and core needle biopsy yield small samples with limited ability to perform flow cytometry and chromosomal analysis; most pediatric hematologists and pathologists prefer excisional biopsy. (However, a retrospective study by Sher-Locketz et al reported that fine-needle aspiration biopsy, as performed through an efficient laboratory-managed service, proved to be an acceptable replacement for surgical biopsy in the triage of pediatric lymphadenopathy. [26] )

Excisional biopsy also has limitations and may yield a definitive diagnosis in only 40-60% of patients because of inadequate specimen size, improper handling, or node-sampling error (eg, Hodgkin lymphoma); sampling more accessible nodes may miss the underlying malignancy.

The surgeon should therefore biopsy larger, firmer, and most recently enlarging nodes, even if it is technically difficult, with appropriate handling of the specimen. If an excisional biopsy does not reveal the diagnosis, a second biopsy may be indicated.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a widespread technique for tissue sampling from hilar and mediastinal lymph nodes; however, the predominant finding in routine care is a nondiagnostic cytology in more than 70% of patients. [27]

A multicenter study by Dhooria et al indicated that, as in adults, EBUS-TBNA and endoscopic ultrasonography with an echobronchoscope-guided fine-needle aspiration (EUS-B-FNA) can be safely and effectively used in children with mediastinal lymphadenopathy, providing a good diagnostic yield. [28]

A retrospective study by Wilczynski et al suggested that ultrasonographically guided full-core needle biopsy (UFCNB) is an effective alternative to whole surgical lymph node excision in the diagnosis of lymphadenopathy of unknown origin. The investigators found UFCNB to have a sensitivity of 94.4%, a specificity of 97.8%, and a diagnostic accuracy of 95.0%, with regard to the condition. [29]


Histologic Findings

Histiologic findings depend on the underlying etiology of the lymphadenopathy. Nonspecific changes consistent with reactive adenopathy are often the only findings. This is helpful in ruling out malignancy, histiocytoses, granulomatous disorders, and storage diseases. Specific infections can be diagnosed if tissues are appropriately stained.

When examining the tissue, histiologic findings are often inadequate. Flow cytometric and chromosomal analysis may provide critical information to permit a diagnosis to be established.



Staging is relevant only when a specific malignancy is diagnosed as the etiology of lymphadenopathy.